Migraine
Conditions
Keywords
Healthy, Volunteer, Pharmacokinetics
Brief summary
This is a single-center, open-label, randomized, four-way crossover study. Each subject will receive each of the four study treatments once, followed by in-clinic monitoring and extensive blood sample collection for pharmacokinetic analysis. Dosing will occur approximately 48 hours apart, until completion of dosing in randomized order per the treatment sequence tables. Plasma samples from the dosing days will be sent to the analytical laboratory for analysis and tolerability for each of the dose levels will be summarized. After completion of the four dosing days, subjects will be assessed one final time and dismissed from the study.
Detailed description
This is a single-center, open-label, randomized, four-way crossover study to compare the pharmacokinetics, safety and tolerability of: M207 3.8 mg administered to the upper arm to M207 3.8 mg administered to the thigh, particularly with respect to skin irritation (erythema, edema, bruising, bleeding): M207 3.8 mg worn for 30 minutes on the upper arm to M207 3.8 mg worn for 1 hour on the upper arm; and M207 3.8 mg to intranasal zolmitriptan 2.5 mg. Each subject will receive each of the four study treatments once, followed by in-clinic monitoring and extensive blood sample collection for pharmacokinetic analysis. M207 application sites will be observed for erythema, edema, bruising, and bleeding at various timepoints throughout the study. Dosing will occur approximately 48 hours apart, until completion of dosing in randomized order per the treatment sequence tables. Plasma samples from the dosing days will be sent to the analytical laboratory for analysis and tolerability for each of the dose levels will be summarized. After completion of the four dosing days, subjects will be assessed one final time and dismissed from the study.
Interventions
DRUGA: M207 3.8mg, 30 min, upper arm
A: M207 3.8 mg administered as two 1.9 mg patches, 30 min wear time (upper arm application)
DRUGB: M207 3.8 mg, 30 min, thigh
B: M207 3.8 mg administered as two 1.9 mg patches, 30 min wear time (thigh application)
DRUGC: M207 3.8 mg, 1 hr, upper arm
C: M207 3.8 mg administered as two 1.9 mg patches, 1 hour wear time (upper arm application)
DRUGD:zolmitriptan nasal spray
D: 2.5 mg/0.1 mL intranasal zolmitriptan
Sponsors
Zosano Pharma Corporation
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Randomized, open-label four-way crossover
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
1. Women or men 18 to 50 years of age. 2. Good general health with no clinically significant abnormalities as determined by medical history, physical examination, complete blood count (CBC), blood chemistry, urinalysis, and ECG. 3. Negative urine drug and alcohol screens and negative serum pregnancy tests (for female subjects) at screening. 4. Consent of female subjects to use a medically effective method of contraception throughout the entire study period and for 30 days after the subject completes the study. Medically effective methods of contraception that may be used by the subject include abstinence, use of diaphragm and spermicide, intrauterine device (IUD), condom and vaginal spermicide, hormonal contraceptives (subjects must be stable on hormonal contraceptives for at least the prior 3 months), surgical sterilization, and post-menopausal (≥ 2 years of amenorrhea). 5. Ability to read, understand, and provide written informed consent that they understand the purpose of the study and procedures required for the study before enrolling in the study, and willingness to comply with all study procedures and restrictions.
Exclusion criteria
1. Evidence of significant history of hepatic, reproductive, gastrointestinal, renal, bleeding, or hematological disorders including coagulation, pulmonary, neurological, respiratory, endocrine, or cardiovascular system abnormalities (especially hypertension, peripheral vascular disease, coronary artery disease, transient ischemic attacks, or cardiac rhythm abnormalities), psychiatric disorders, acute infection, or other conditions that would interfere with study participation or with the absorption, distribution, metabolism, or excretion of drugs. 2. Presence of two or more risk factors for cardiovascular disease (family history of premature heart disease, hyperlipidemia, or hypertension) 3. Any contraindication to zolmitriptan administration including: * History of coronary artery disease or coronary vasospasm * Symptomatic Wolf-Parkinson-White syndrome or other cardiac accessory conduction pathway disorders * History of stroke, transient ischemic attack, or hemiplegic or basilar migraine * Peripheral Vascular Disease * Ischemic bowel disease * Uncontrolled hypertension * Any history of hepatic impairment 4. History of contact dermatitis or known dermatological disorders that would interfere with the study procedures or assessments 5. Planned participation in activities which cause inflammation, irritation, sunburn, lesions, or tattoos at the intended application sites from 2 weeks prior to screening through their last day of study participation 6. Use of warfarin within 1 month prior to the first dose or heparin within 1 week prior to study drug administration 7. Use of prescription and over the counter medications other than the following: * Hormone Replacement Therapy (HRT) * Birth control pills, patches, injections, or implants (all hormonal contraceptives) are allowed provided the dose has been stable for at least one month prior to screening and may be continued throughout the study * Antihistamines * Intermittently used NSAIDS * Acetaminophen if medically necessary (not more than 2 g/day) * Exceptions may be allowed on a case by case basis 8. Subjects who have a known allergy or sensitivity to zolmitriptan or its derivatives or formulations 9. Known allergy or sensitivity to tapes, adhesives, or zolmitriptan 10. Regular or recent intake of prescription drugs, particularly drugs with an influence on blood pressure. 11. Use of any other investigational compound within one month of planned study drug dosing 12. On-going drug or alcohol abuse, or history of either deemed to be clinically significant by the investigator 13. Systolic BP (measured after remaining sitting for 5 minutes) greater than 140 mmHg and diastolic BP greater than 90 mmHg at screening 14. History of nasal pathology (e.g., polyps) or abnormal nasal exam 15. Body Mass Index (BMI) greater than 35 kg/m2 16. If, in the opinion of the investigator, the subject is not suitable for the study 17. Any positive urine drug screen result or alcohol breath test
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | pre-dose, 2, 5, 10, 15, 20, 30, 45, 60, 90 minutes, 2, 4, 8, 12, 24 hours post-dose | maximum observed plasma concentration |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events | 24 hours | number of subjects that experienced at least one adverse event |
| t(1/2) | pre-dose, 2, 5, 10, 15, 20, 30, 45, 60, 90 minutes, 2, 4, 8, 12, 24 hours post-dose | apparent half-life |
Countries
United States
Participant flow
Pre-assignment details
4-way crossover, each subject randomized to receive A, B, C, and D in one of four sequences. A: M207 3.8 mg, two 1.9 mg patches, 30 min, upper arm B: M207 3.8 mg, two 1.9 mg patches, 30 min, thigh C: M207 3.8 mg, two 1.9 mg patches, 1 hr, upper arm D: Intranasal zolmitriptan 2.5 mg One subject randomized to CADB was given ABCD.
Participants by arm
| Arm | Count |
|---|---|
| Entire Study Population Each subject received each of the four treatments below in one of four treatment sequences.
A: M207 3.8 mg administered as two 1.9 mg patches, 30 min wear time (upper arm application) B: M207 3.8 mg administered as two 1.9 mg patches, 30 min wear time (thigh application) C: M207 3.8 mg administered as two 1.9 mg patches, 1 hour wear time (upper arm application) D: Intranasal zolmitriptan 2.5 mg | 24 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 |
Baseline characteristics
| Characteristic | Entire Study Population |
|---|---|
| Age, Continuous | 36.2 years STANDARD_DEVIATION 9.44 |
| BMI | 26.93 kg/m^2 STANDARD_DEVIATION 3.264 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 15 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 7 Participants |
| Region of Enrollment United States | 24 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 23 | 0 / 24 | 0 / 23 |
| other Total, other adverse events | 4 / 23 | 3 / 23 | 1 / 24 | 1 / 23 |
| serious Total, serious adverse events | 0 / 23 | 0 / 23 | 0 / 24 | 0 / 23 |
Outcome results
Primary
Cmax
maximum observed plasma concentration
Time frame: pre-dose, 2, 5, 10, 15, 20, 30, 45, 60, 90 minutes, 2, 4, 8, 12, 24 hours post-dose
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | Cmax | 9180.9 pg/mL | Standard Deviation 4066.1 |
| Treatment B | Cmax | 5925.9 pg/mL | Standard Deviation 2353.3 |
| Treatment C | Cmax | 15224.3 pg/mL | Standard Deviation 12972.9 |
| Treatment D | Cmax | 3758.3 pg/mL | Standard Deviation 1711.6 |
Secondary
Adverse Events
number of subjects that experienced at least one adverse event
Time frame: 24 hours
Population: Subjects who received treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Treatment A | Adverse Events | 4 Participants |
| Treatment B | Adverse Events | 3 Participants |
| Treatment C | Adverse Events | 1 Participants |
| Treatment D | Adverse Events | 1 Participants |
Secondary
t(1/2)
apparent half-life
Time frame: pre-dose, 2, 5, 10, 15, 20, 30, 45, 60, 90 minutes, 2, 4, 8, 12, 24 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment A | t(1/2) | 2.692 hours | Standard Deviation 0.486 |
| Treatment B | t(1/2) | 2.975 hours | Standard Deviation 1.217 |
| Treatment C | t(1/2) | 2.959 hours | Standard Deviation 0.998 |
| Treatment D | t(1/2) | 4.545 hours | Standard Deviation 1.535 |